In the above-noted copending application, the disclosure of which is incorporated herein by reference, a process for microencapsulating labile biological materials in a semipermeable membrane is disclosed. That process comprises an improvement in the well-known microencapsulation procedure known as interfacial polymerization, which involves forming an emulsion having an aqueous or hydrophilic discontinuous phase containing one of two complementary monomers and the material to be encapsulated and a hydrophobic continuous phase. When the complementary monomer is added to the emulsion, polymerization occurs at the interphase about the typically 5-200 micron diameter aqueous droplets.
In accordance with the invention of the above-mentioned application, easily denatured biological material such as enzymes, hemoglobin, antigens, antibodies and the like may be microencapsulated such that they retain their biological activity if, for example, the aqueous discontinuous phase is buffered with carbon dioxide to have a pH of between about 8 and 9, and if the second monomer is the continuous phase of the emulsion is added incrementally so that its concentration at any given time is maintained at a low level. Furthermore, the above-referenced application discloses that microcapsules of a selected, relatively uniform porosity (semipermeability) can be produced in a two-stage procedure wherein the interfacial polymerization is interrupted by removing raw, poorly formed, macroporous microcapsules from the emulsion, the microcapsules are washed, and then resuspended in a different solvent having a lower affinity for the aqueous phase bound first monomer than that of the original solvent. When a second portion of the second monomer is added to the new continuous phase, further polymerization occurs preferentially within the macroporous structure of the raw capsules, and strong, semipermeable membranes are produced.
By utilizing these and other teachings in the application, it is possible to immobilize high molecular weight biological materials such as enzymes and the like within a membrane having pores too small to allow passage of the encapsulated material yet small enough to allow diffusion of lower molecular weight materials such as the enzyme's substrate.